Technetium-99m (99mTc) is a kind of radionuclides which has been most widely used in diagnostic radiopharmaceuticals owing to its comparatively short half-life (6 hour) and gamma ray emission of 140 keV which is appropriate for obtaining a gamma image along with low prices and ready availability. The 99mTc forms a complex by reacting with a compound having a lone electron pair such as isocyanate group, amine group, carboxyl group, thiol group, etc, which is used as an imaging agent or a labeling agent for various organs or tissues including lung, liver, brain, etc.
Reduction of technetium has to be performed prior to the reaction of pertechnetate and ligand to form a radioactive complex. At this time, reduction is performed by electrolysis or by a reducing agent such as SnCl2.2H2O, Fe++, ascorbate containing Fe++, formamidinesulfinic acid, sodium borohydride, etc is used. Among those reducing agents, SnCl2.2H2O is most popular.
Among many 99mTc complexes, 99mTc—Sb2S3 nanocolloid (technetium-99m labeled antimony trisulfide nanocolloid, 99mTc-ASC) has been widely used for lymphoscintigraphy or bone marrow scintigraphy.
The 99mTc—Sb2S3 nanocolloid is formed by the reaction of pertechnetate and Sb2S3 nanocolloid in the presence of a reducing agent. As a reducing agent, SnCl2, NaBH4 or HCl can be used and actually HCl is preferred. SnCl2 is the most popular reducing agent but has a problem of producing tin colloid during the preparation processes of 99mTc—Sb2S3 nanocolloid. However, NaBH4 has a problem that stability changes according to pH.
The 99mTc—Sb2S3 nanocolloid has been prepared by the conventional method as follows. Freeze-dried Sb2S3 nanocolloid and Na99mTcO4 are mixed together in the presence of HCl, followed by heating for 30 minutes. Then, a buffer is added and pH is adjusted to 6-7. The size of the obtained 99mTc—Sb2S3 nanocolloid particle is 5-20 nm (mostly 7-15 nm).
As explained above, the conventional preparation method for 99mTc—Sb2S3 nanocolloid requires HCl as a reducing agent, and it has to be heated for reaction. Such reaction at high temperature brings difficulties in handling and often causes breakdown of chemical bond. Besides, pH has to be re-adjusted to neutral for the administration to a patient.